NM_014498.5:c.1645A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014498.5(GOLIM4):​c.1645A>C​(p.Asn549His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GOLIM4
NM_014498.5 missense

Scores

13
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69
Variant links:
Genes affected
GOLIM4 (HGNC:15448): (golgi integral membrane protein 4) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a type II Golgi-resident protein. It may process proteins synthesized in the rough endoplasmic reticulum and assist in the transport of protein cargo through the Golgi apparatus. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GOLIM4NM_014498.5 linkc.1645A>C p.Asn549His missense_variant Exon 13 of 16 ENST00000470487.6 NP_055313.1 O00461

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GOLIM4ENST00000470487.6 linkc.1645A>C p.Asn549His missense_variant Exon 13 of 16 1 NM_014498.5 ENSP00000417354.1 O00461
GOLIM4ENST00000309027.4 linkc.1561A>C p.Asn521His missense_variant Exon 12 of 15 1 ENSP00000309893.4 F8W785

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1645A>C (p.N549H) alteration is located in exon 13 (coding exon 13) of the GOLIM4 gene. This alteration results from a A to C substitution at nucleotide position 1645, causing the asparagine (N) at amino acid position 549 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Uncertain
0.061
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.60
D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-2.4
N;D
REVEL
Benign
0.23
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.040
D;D
Polyphen
1.0
D;D
Vest4
0.74
MutPred
0.33
Gain of helix (P = 6e-04);.;
MVP
0.74
MPC
0.46
ClinPred
0.97
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.36
gMVP
0.057

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-167742862; API